The Vibrio cholerae QS System
The causative agent of the disease cholera, Vibrio cholerae, infects the small intestine of humans and causes massive diarrhea. Cholera is a devastating disease, especially in developing countries, and it is currently in the 7th pandemic. Like many bacterial pathogens, V. cholerae depends on an intricate cell-cell communication system, called Quorum Sensing (QS), to precisely regulate the timing of production of colonization factors and toxins inside the human host. Furthermore, biofilm formation, genetic exchange and many important cellular processes are controlled by QS. By using a multidisciplinary approach, we focus on elucidating the molecular mechanisms governing QS in V. cholerae and hope to develop new strategies to interfere bacterial communication to control virulence.
Parallel QS signal transduction mechanism in bacteria
We discovered that at least four sensory inputs function in parallel to regulate V. cholerae QS (Fig. 1). Surprisingly, any one of these communication pathways is sufficient to foster host colonization by the pathogen. We are interested in understanding how and why V. cholerae perceives multiple parallel sensory inputs to precisely control its QS behaviors. Do these new signal pathways detect Vibrio-specific signals and prevent interference from other species? Or do they sense common signals that allow interspecies communication?
Figure 1. The Vibro cholerea quorum sensing circuit.
The role of QS in maintaining bacterial community stability
The V. cholerae QS regulon is composed of more than 100 genes, yet our understanding of the role QS plays in V. cholerae physiology is very limited. We found that several QS-controlled small RNAs (sRNAs) are key regulators for maintaining metabolic homeostasis of this pathogen. We are interested in understanding why V. cholerae uses QS to reprogram metabolism, and how such regulation is used to sustain long term community stability and its role in pathogenesis and interspecies competition.
Synthetic strategies for dissecting microbial signal transduction and virulence control
The V. cholerae QS system is composed of phosphorelay systems and RNA regulators that are widely used by bacteria to regulate critical cellular functions (Fig. 1). Thus, this communication system is well-suited for defining the underlying principles governing transmembrane signaling and RNA-based gene regulation. We have identified chemical molecules that perturb the functions of different components in this system and hope to employ these chemical probes to further dissect fundamental problems in prokaryotic signal transduction. The overarching goal is to develop these small molecules into new classes of anti-virulence agents for cholera and perhaps other pathogens.